High prevalence of polycystic ovary syndrome in women born small for gestational age

Abstract

background: There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA).methods: This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirão Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS.results: The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR ¼ 2.44, 95% CI (1.39-4.28)].Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P ¼ 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P ¼ 0.041), but fasting insulinemia was similar in both groups.conclusions: The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

“…Experimental studies in animals (Abbott et al 2002 and clinical observations in human subjects (Melo et al 2010) lend support to the hypothesis that developmental programming by steroid excess plays a role in the development of PCOS and its associated disorders at various stages of life (Jaquet et al 2005) (Fig. 1).…”

“…3). During the third decade of life, this risk can be twice as high in women born SGA as it is in women born AGA (Melo et al 2010). However, PCOS does not occur in all women born SGA (Laitinen et al 2003, Mumm et al 2013, and …”

“…However, studies with experimental animals have found that foetuses with IUGR caused by placental insufficiency or maternal malnutrition were born SGA and that these animals showed a predisposition to developing pathologies in postnatal life after compensatory growth during the first 2 years of life (Bloomfield et al 2003, Reynolds 2012. Clinical data show that compensatory growth might also be associated with the development of comorbidities in humans, such as precocious puberty (Ibáñez et al 1998), SAH (Elting et al 2001), cardiovascular disease (Bonamy et al 2008), type 2 DM, glucose intolerance (Willemsen et al 2008), dyslipidaemia, obesity (Martinez-Aguayo et al 2007), R16 A S Melo and others metabolic syndrome (Jaquet et al 2005) and PCOS (Pandolfi et al 2008, Melo et al 2010, Hizli et al 2012. Thus, children born SGA would exhibit a clinical marker of developmental programming by glucocorticoids associated with the development of PCOS and its associated comorbidities, although SGA may also be constitutional (variation of normal).…”

“…Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disorder with an estimated prevalence of 5-13.9% in women of reproductive age (Norman et al 2007, Melo et al 2010. In addition to causing reproductive disorders (anovulation and infertility), PCOS may or may not have a clinical and metabolic impact that varies according to ethnicity and geographic region (Tian et al 2006, Norman et al 2007.…”

“…Experimental studies show that androgen excess during intra-uterine development may also be associated with intra-uterine growth restriction (IUGR) (Beckett et al 2014), hyperinsulinaemia, visceral obesity in childhood and PCOS-like reproductive manifestations in women of reproductive age , Padmanabhan & Veiga-Lopez 2011. Notwithstanding this association, individuals who apparently did not undergo developmental programming (subjects with birth weights appropriate for their gestational age (AGA) and daughters of women without hyperandrogenism during pregnancy) can also develop PCOS (Melo et al 2010). This observation suggests that genetic variation and environmental factors play important roles in the development of PCOS.…”